Insulin-like growth factor-I ("IGF-I;" also known as "somatomedin-C") is a mammalian growth factor essential for normal growth and development. It has insulin-like effects on muscle and adipose tissue, and it has mitogenic effects on several cell types. IGF-I has a variety of clinical uses. For example, it may be used to enhance the survival of neurons such as non-mitotic cholinergic neurons (Lewis et al, U.S. Pat. No. 5,093,317).
The complete amino acid sequence of the human IGF-I protein is known, and DNA encoding human IGF-I has been cloned and expressed in E. coli and yeast (see, e.g., Brierley et al., U.S. Pat. No. 5,324,639). The human IGF-I protein consists of a single 70-amino acid polypeptide that includes six cysteine residues, all of which participate in the formation of three intrachain disulfide bonds (Axelsson et al., Eur. J. Biochem. 206:987 (1992)). The three disulfide bonds, with all six cysteine residues properly paired, are necessary in order for IGF-I to have its correct (i.e., natural) tertiary structure. Upon reduction and reoxidation of the disulfide bonds, IGF-I can refold in various ways, forming as many as 15 monomeric configurations (Meng et al., J. Chrom. 433:183 (1988)). In addition, IGF-I polypeptides can interact with each other to form multimeric structures. Processes for obtaining purified, correctly folded IGF-I have been published (see, e.g., Holtz et al., U.S. Pat. No. 5,231,178 ("Holtz"); Chang et al., U.S. Pat. No. 5,288,931; and Hart et al., Biotech. Appl. Biochem. 20:217 (1994)).